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A secreted morphogen originally discovered in Drosophila; various mammalian homologues have subsequently been identified (sonic hedgehog (462 aa), Indian hedgehog (411 aa), and desert hedgehog (396 aa), all of which are involved in patterning of the embryo. The protein precursors are autoprocessed to produce ~20-kDa N-terminal portions that are active in the hedgehog signalling pathway which, if perturbed, can disrupt organ development and cause various degenerative and neoplastic human diseases. Further processing of the active portion involves palmitoylation and the addition of cholesterol. The primary receptor is the twelve-transmembrane protein patched (Ptc) but a second receptor, a seven-transmembrane protein called smoothened (Smo), actually transduces the signal. Smo is held in a dormant state by Ptc in normal cells and Ptc is internalized when it binds hedgehog, thereby releasing the inhibition. The signal is up-regulated by the gli oncogene family of transcription factors which activate forkhead box (FOX) transcription factors in a complex cascade. See hedgehog signalling complex.

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